YH001 + Envafolimab for Sarcoma

Recruiting at 5 trial locations

Overseen By James Freddo, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Tracon Pharmaceuticals Inc.

Must not be taking: Corticosteroids, Immunosuppressives

Disqualifiers: GIST, Desmoid tumors, Coronary syndromes, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 6

15 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a multicenter, open label, Phase 1/2 study of YH001 initially given in combination with envafolimab, and then given in combination with envafolimab plus doxorubicin in patients with advanced or metastatic sarcoma, followed by Phase 2 cohorts of patients with select histologies of advanced or metastatic sarcoma.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be on systemic corticosteroids or other immunosuppressive medications within 14 days before joining the study.

What data supports the effectiveness of the drug YH001 + Envafolimab for sarcoma?

Research on similar drugs, like nivolumab and ipilimumab, shows that immune checkpoint inhibitors (drugs that help the immune system attack cancer cells) have been tested in sarcoma with some promising results. These studies suggest that combining different immune-targeting drugs might help treat sarcoma by enhancing the body's immune response against the cancer. ^{1 2 3 4 5}

What makes the drug YH001 + Envafolimab unique for treating sarcoma?

The drug YH001 + Envafolimab is unique because Envafolimab is the first and only PD-L1 antibody that can be injected under the skin, making it more convenient than other treatments that require intravenous administration. This combination targets specific proteins involved in cancer growth, potentially offering a new approach for patients with sarcoma who have limited treatment options. ^{1 6 7 8 9}

Research Team

James Freddo, MD

Principal Investigator

Medical Monitor

Eligibility Criteria

Adults with advanced or metastatic sarcoma, except for UPS or MFS types, who haven't had immune checkpoint inhibitors or doxorubicin. They should have measurable disease and good organ function. Women must not be pregnant and agree to birth control; men must use a condom if not sterile.

Inclusion Criteria

I am willing and able to give my consent to participate in the study.

I am either not able to have children due to surgery or a medical condition, or I can have children but agree to use birth control.

My organs are working well.

Exclusion Criteria

I haven't taken steroids or immunosuppressants in the last 14 days.

Known allergy to any component of any study drug that the patient would receive if enrolled into this study

I have not had a heart attack or other serious heart problems in the last 6 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 Treatment

YH001 is given in combination with envafolimab, and then with envafolimab plus doxorubicin every 3 weeks

8 months

Visits every 3 weeks

Phase 2 Treatment

YH001 is given in combination with envafolimab, with or without doxorubicin, in patients with select histologies of advanced or metastatic sarcoma

22 months

Visits every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-6 months

Treatment Details

Interventions

• Doxorubicin
• Envafolimab
• YH001

Trial Overview The study is testing YH001 in combination with Envafolimab, and then adding Doxorubicin for certain patients. It's an open-label trial meaning everyone knows what treatment they're getting, starting with Phase 1/2 followed by specific patient groups in Phase 2.

Participant Groups

Group I: P2: Sarcoma Subtype 4 RP2D YH001 + Dose 1 Envafolimab + Doxorubicin Q3WK Experimental Treatment 3 Interventions

Recommended Phase 2 Dose of YH001 in combination with Dose 1 of Envafolimab every 3 weeks and Doxorubicin every 3 weeks for a maximum of 6 doses

Group II: P2: Sarcoma Subtype 3 RP2D YH001 + Dose 1 Envafolimab + Doxorubicin Q3WK Experimental Treatment 3 Interventions

Recommended Phase 2 Dose of YH001 in combination with Dose 1 of Envafolimab every 3 weeks and Doxorubicin every 3 weeks for a maximum of 6 doses

Group III: P2: Sarcoma Subtype 2 RP2D YH001 + Dose 1 Envafolimab Q3WK Experimental Treatment 2 Interventions

Recommended Phase 2 Dose of YH001 in combination with Dose 1 of Envafolimab every 3 weeks

Group IV: P2: Sarcoma Subtype 1 RP2D YH001 + Dose 1 Envafolimab Q3WK Experimental Treatment 2 Interventions

Recommended Phase 2 Dose of YH001 in combination with Dose 1 of Envafolimab every 3 weeks

Group V: P1 Cohort 2B: Dose 2 YH001 + Dose 1 Envafolimab + Doxorubicin Q3WK Experimental Treatment 3 Interventions

Dose 1 of YH001 will be dosed in combination with Dose 1 of Envafolimab with Doxorubicin every 3 weeks.

Group VI: P1 Cohort 2A: Dose 2 YH001 + Dose 1 Envafolimab Q3WK Experimental Treatment 2 Interventions

Dose 1 of YH001 will be dosed in combination with Dose 1 Envafolimab every 3 weeks.

Group VII: P1 Cohort 1B: Dose 1 YH001 + Dose 1 Envafolimab + Doxorubicin Q3WK Experimental Treatment 3 Interventions

Dose 1 of YH001 will be dosed in combination with Dose 1 of Envafolimab with Doxorubicin every 3 weeks.

Group VIII: P1 Cohort 1A: Dose 1 YH001 + Dose 1 Envafolimab Q3WK Experimental Treatment 2 Interventions

Dose 1 of YH001 will be dosed in combination with Dose 1 Envafolimab every 3 weeks.

Who Is Running the Clinical Trial?

Tracon Pharmaceuticals Inc.

Lead Sponsor

Trials

22

Recruited

1,000+

Findings from Research

In a phase 2 study involving 85 patients with metastatic sarcoma, the combination of nivolumab and ipilimumab showed a higher confirmed response rate (16%) compared to nivolumab alone (5%), indicating that the combination therapy may be more effective for certain sarcoma subtypes.

While both treatments had manageable safety profiles, serious treatment-related adverse events occurred in 19% of patients receiving nivolumab and 26% in those receiving the combination therapy, suggesting that while the combination is promising, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab with or without ipilimumab treatment for metastatic sarcoma (Alliance A091401): two open-label, non-comparative, randomised, phase 2 trials. D'Angelo, SP., Mahoney, MR., Van Tine, BA., et al.[2021]

In a phase 2 trial involving 62 patients with advanced or metastatic sarcoma, the combination of durvalumab and tremelimumab showed a promising progression-free survival rate of 49% at 12 weeks, indicating its potential efficacy as a treatment option.

While the treatment was generally active, it was associated with some serious adverse events, including one case of grade 5 pneumonitis and colitis, highlighting the need for careful monitoring of patients during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab plus tremelimumab in advanced or metastatic soft tissue and bone sarcomas: a single-centre phase 2 trial. Somaiah, N., Conley, AP., Parra, ER., et al.[2023]

The combination of the mTOR inhibitor nab-sirolimus and the immune checkpoint inhibitor nivolumab was found to be safe for patients with advanced sarcoma, with a maximum-tolerated dose established at 100 mg/m2 and no unexpected adverse events reported.

While the treatment did not improve overall outcomes compared to nivolumab alone, the best responses were observed in patients with specific genetic mutations, such as PTEN loss and TSC2 mutation, indicating potential for biomarker-driven approaches in future research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase I/II Investigation of Safety and Efficacy of Nivolumab and nab-Sirolimus in Patients With a Variety of Tumors With Genetic Mutations in the mTOR Pathway. Gordon, EM., Angel, NL., Omelchenko, N., et al.[2023]

Envafolimab, the first subcutaneously injectable PD-L1 antibody, was well tolerated in a Phase 1 trial with 35 Japanese patients, showing no dose-limiting toxicities and a safety profile similar to existing treatments.

The overall response rate was 11.4% and the disease control rate was 34.3%, indicating that envafolimab is effective and offers a more convenient dosing schedule compared to traditional intravenous PD-1/PD-L1 inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of envafolimab (KN035), a novel subcutaneous single-domain anti-PD-L1 monoclonal antibody, in Japanese patients with advanced solid tumors. Shimizu, T., Nakajima, TE., Yamamoto, N., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Nivolumab with or without ipilimumab treatment for metastatic sarcoma (Alliance A091401): two open-label, non-comparative, randomised, phase 2 trials. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Contemporary Therapy for Advanced Soft-Tissue Sarcomas in Adults: A Review. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Durvalumab plus tremelimumab in advanced or metastatic soft tissue and bone sarcomas: a single-centre phase 2 trial. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Nivolumab and sunitinib combination in advanced soft tissue sarcomas: a multicenter, single-arm, phase Ib/II trial. [2021]

5. Greece pubmed.ncbi.nlm.nih.gov

A Phase I/II Investigation of Safety and Efficacy of Nivolumab and nab-Sirolimus in Patients With a Variety of Tumors With Genetic Mutations in the mTOR Pathway. [2023]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Envafolimab: First Approval. [2022]

7. Egypt pubmed.ncbi.nlm.nih.gov

A Pilot Study of Anti-CTLA4 Antibody Ipilimumab in Patients with Synovial Sarcoma. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Phase I study of envafolimab (KN035), a novel subcutaneous single-domain anti-PD-L1 monoclonal antibody, in Japanese patients with advanced solid tumors. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Bispecific Antibody PD-L1 x CD3 Boosts the Anti-Tumor Potency of the Expanded Vγ2Vδ2 T Cells. [2021]